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During the ongoing COVID-19 pandemic, PCR testing and antigen tests have proven critical for helping to stem the spread of its causative agent, SARS-CoV-2. However, these methods suffer from either general applicability and/or sensitivity. Moreover, the emergence of variant strains creates the need for flexibility to correctly and efficiently diagnose the presence of substrains. To address these needs we developed the diagnostic test ADESSO (Accurate Detection of Evolving SARS-CoV-2 through SHERLOCK (Specific High Sensitivity Enzymatic Reporter UnLOCKing) Optimization) which employs Cas13 to diagnose patients in 1 h without sophisticated equipment. Using an extensive panel of clinical samples, we demonstrate that ADESSO correctly identifies infected individuals at a sensitivity and specificity comparable to RT-qPCR on extracted RNA and higher than antigen tests for unextracted samples. Altogether, ADESSO is a fast, sensitive and cheap method that can be applied in a point of care setting to diagnose COVID-19 and can be quickly adjusted to detect new variants.

With the coronavirus disease 19 (COVID-19) pandemic now deep into its second year, widespread testing for the detection of the causative severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is fundamental. The gold standard reverse transcription quantitative PCR (RT-qPCR) cannot keep up with the high demand alone, therefore alternative diagnostic tests are needed. Here we present ADESSO (Accurate Detection of Evolving SARS-CoV-2 through SHERLOCK Optimisation), an optimised version of the CRISPR-based SHERLOCK (Specific High-sensitivity Enzymatic Reporter unLOCKing) assay. After an extensive validation on 983 clinical samples, we demonstrated that ADESSO has a sensitivity of 96% and a specificity of 100% on extracted RNA, comparable to RT-qPCR. Its performance on unextracted samples still allows the detection of the more infectious 75% of the COVID-19 positive population, making it suitable for point-of-care (POC) testing. Interestingly, our in parallel comparison of 390 matching swab and gargle samples showed consistently lower viral loads in gargle specimens. We also validated ADESSO for the detection of the B.1.1.7 variant and demonstrated that ADESSO is adaptable to any variant of concern in less than one week, a critical feature now that worrisome SARS-CoV-2 variants are spreading all around the world.